Fast skeletal myosin binding protein-C expression exacerbates dysfunction in heart failure

Andreadou I, Ghigo A, Nikolaou P-E, Swirski FK, Thackeray JT, Heusch G, Vilahur G (2025) Immunometabolism in heart failure. Nat Rev Cardiol 22:751–772. https://doi.org/10.1038/s41569-025-01165-8

Article  PubMed  Google Scholar 

Barefield D, Sadayappan S (2010) Phosphorylation and function of cardiac myosin binding protein-C in health and disease. J Mol Cell Cardiol 48:866–875. https://doi.org/10.1016/j.yjmcc.2009.11.014

Article  CAS  PubMed  Google Scholar 

Barefield DY, McNamara JW, Lynch TL, Kuster DWD, Govindan S, Haar L, Wang Y, Taylor EN, Lorenz JN, Nieman ML, Zhu G, Luther PK, Varró A, Dobrev D, Ai X, Janssen PML, Kass DA, Jones WK, Gilbert RJ, Sadayappan S (2019) Ablation of the calpain-targeted site in cardiac myosin binding protein-C is cardioprotective during ischemia-reperfusion injury. J Mol Cell Cardiol 129:236–246. https://doi.org/10.1016/j.yjmcc.2019.03.006

Article  CAS  PubMed  PubMed Central  Google Scholar 

Farrell E, Armstrong AE, Grimes AC, Naya FJ, de Lange WJ, Ralphe JC (2018) Transcriptome analysis of cardiac hypertrophic growth in MYBPC3-null mice suggests early responders in hypertrophic remodeling. Front Physiol. https://doi.org/10.3389/fphys.2018.01442

Article  PubMed  PubMed Central  Google Scholar 

Figtree GA, Broadfoot K, Casadei B, Califf R, Crea F, Drummond GR, Freedman JE, Guzik TJ, Harrison D, Hausenloy DJ, Hill JA, Januzzi JL, Kingwell BA, Lam CSP, MacRae CA, Misselwitz F, Miura T, Ritchie RH, Tomaszewski M, Wu JC, Xiao J, Zannad F (2021) A call to action for new global approaches to cardiovascular disease drug solutions. Eur Heart J 42:1464–1475. https://doi.org/10.1093/eurheartj/ehab068

Article  PubMed  Google Scholar 

Fougerousse F, Delezoide AL, Fiszman MY, Schwartz K, Beckmann JS, Carrier L (1998) Cardiac myosin binding protein C gene is specifically expressed in heart during murine and human development. Circ Res 82:130–133. https://doi.org/10.1161/01.res.82.1.130

Article  CAS  PubMed  Google Scholar 

Fu X, Khalil H, Kanisicak O, Boyer JG, Vagnozzi RJ, Maliken BD, Sargent MA, Prasad V, Valiente-Alandi I, Blaxall BC, Molkentin JD (2018) Specialized fibroblast differentiated states underlie scar formation in the infarcted mouse heart. J Clin Invest 128:2127–2143. https://doi.org/10.1172/jci98215

Article  PubMed  PubMed Central  Google Scholar 

Gautel M, Fürst DO, Cocco A, Schiaffino S (1998) Isoform transitions of the myosin binding protein C family in developing human and mouse muscles: lack of isoform transcomplementation in cardiac muscle. Circ Res 82:124–129. https://doi.org/10.1161/01.res.82.1.124

Article  CAS  PubMed  Google Scholar 

Hamdani N, Kooij V, van Dijk S, Merkus D, Paulus WJ, Remedios C, Duncker DJ, Stienen GJM, van der Velden J (2007) Sarcomeric dysfunction in heart failure. Cardiovasc Res 77:649–658. https://doi.org/10.1093/cvr/cvm079

Article  CAS  PubMed  Google Scholar 

Hoshijima M, Chien KR (2002) Mixed signals in heart failure: cancer rules. J Clin Invest 109:849–855. https://doi.org/10.1172/JCI15380

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kampourakis T, Yan Z, Gautel M, Sun YB, Irving M (2014) Myosin binding protein-C activates thin filaments and inhibits thick filaments in heart muscle cells. Proc Natl Acad Sci U S A 111:18763–18768. https://doi.org/10.1073/pnas.1413922112

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kane LA, Neverova I, Van Eyk JE (2007) Subfractionation of heart tissue. In: Vivanco F (ed) Cardiovascular proteomics: methods and protocols. Humana Press, Totowa, NJ, p p 87-90

Google Scholar 

Kensler RW, Craig R, Moss RL (2017) Phosphorylation of cardiac myosin binding protein C releases myosin heads from the surface of cardiac thick filaments. Proc Natl Acad Sci U S A 114:E1355-e1364. https://doi.org/10.1073/pnas.1614020114

Article  CAS  PubMed  PubMed Central  Google Scholar 

Korte FS, McDonald KS, Harris SP, Moss RL (2003) Loaded shortening, power output, and rate of force redevelopment are increased with knockout of cardiac myosin binding protein-C. Circ Res 93:752–758. https://doi.org/10.1161/01.Res.0000096363.85588.9a

Article  CAS  PubMed  Google Scholar 

Li A, Nelson SR, Rahmanseresht S, Braet F, Cornachione AS, Previs SB, O’Leary TS, McNamara JW, Rassier DE, Sadayappan S, Previs MJ, Warshaw DM (2019) Skeletal MyBP-C isoforms tune the molecular contractility of divergent skeletal muscle systems. Proc Natl Acad Sci USA 116:21882–21892. https://doi.org/10.1073/pnas.1910549116

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li M, Parker BL, Pearson E, Hunter B, Cao J, Koay YC, Guneratne O, James DE, Yang J, Lal S, O’Sullivan JF (2020) Core functional nodes and sex-specific pathways in human ischaemic and dilated cardiomyopathy. Nat Commun 11:2843. https://doi.org/10.1038/s41467-020-16584-z

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lin B, Govindan S, Lee K, Zhao P, Han R, Runte KE, Craig R, Palmer BM, Sadayappan S (2013) Cardiac myosin binding protein-C plays no regulatory role in skeletal muscle structure and function. PLoS ONE 8:e69671. https://doi.org/10.1371/journal.pone.0069671

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lin BL, Li A, Mun JY, Previs MJ, Previs SB, Campbell SG, Dos Remedios CG, Tombe PP, Craig R, Warshaw DM, Sadayappan S (2018) Skeletal myosin binding protein-C isoforms regulate thin filament activity in a Ca(2+)-dependent manner. Sci Rep 8:2604. https://doi.org/10.1038/s41598-018-21053-1

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lu P, Wu B, Feng X, Cheng W, Kitsis RN, Zhou B (2022) Cardiac myosin heavy chain reporter mice to study heart development and disease. Circ Res 131:364–366. https://doi.org/10.1161/CIRCRESAHA.122.321461

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lynch TLt, Kumar M, McNamara JW, Kuster DWD, Sivaguru M, Singh RR, Previs MJ, Lee KH, Kuffel G, Zilliox MJ, Lin BL, Ma W, Gibson AM, Blaxall BC, Nieman ML, Lorenz JN, Leichter DM, Leary OP, Janssen PML, de Tombe PP, Gilbert RJ, Craig R, Irving T, Warshaw DM, Sadayappan S (2021) Amino terminus of cardiac myosin binding protein-C regulates cardiac contractility. J Mol Cell Cardiol 156:33–44. https://doi.org/10.1016/j.yjmcc.2021.03.009

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ma X, Gao L, Karamanlidis G, Gao P, Lee CF, Garcia-Menendez L, Tian R, Tan K (2015) Revealing pathway dynamics in heart diseases by analyzing multiple differential networks. PLoS Comput Biol 11:e1004332. https://doi.org/10.1371/journal.pcbi.1004332

Article  CAS  PubMed  PubMed Central  Google Scholar 

Martini E, Kunderfranco P, Peano C, Carullo P, Cremonesi M, Schorn T, Carriero R, Termanini A, Colombo FS, Jachetti E, Panico C, Faggian G, Fumero A, Torracca L, Molgora M, Cibella J, Pagiatakis C, Brummelman J, Alvisi G, Mazza EMC, Colombo MP, Lugli E, Condorelli G, Kallikourdis M (2019) Single-cell sequencing of mouse heart immune infiltrate in pressure overload–driven heart failure reveals extent of immune activation. Circulation 140:2089–2107. https://doi.org/10.1161/CIRCULATIONAHA.119.041694

Article  CAS  PubMed  Google Scholar 

McConnell BK, Jones KA, Fatkin D, Arroyo LH, Lee RT, Aristizabal O, Turnbull DH, Georgakopoulos D, Kass D, Bond M, Niimura H, Schoen FJ, Conner D, Fischman DA, Seidman CE, Seidman JG (1999) Dilated cardiomyopathy in homozygous myosin-binding protein-C mutant mice. J Clin Invest 104:1235–1244. https://doi.org/10.1172/jci7377

Article  CAS  PubMed  PubMed Central  Google Scholar 

McNamara JW, Sadayappan S (2018) Skeletal myosin binding protein-C: an increasingly important regulator of striated muscle physiology. Arch Biochem Biophys 660:121–128. https://doi.org/10.1016/j.abb.2018.10.007

Article  CAS  PubMed  PubMed Central  Google Scholar 

McNamara JW, Singh RR, Sadayappan S (2019) Cardiac myosin binding protein-C phosphorylation regulates the super-relaxed state of myosin. Proc Natl Acad Sci U S A 116:11731–11736. https://doi.org/10.1073/pnas.1821660116

Article  CAS  PubMed 

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